Synergistic biocidal compositions and methods



United States Patent 0 3,417,185 SYNERGISTIC BIOCIDAL COMPOSITIONS AND METHODS Robert John Herschier, Camas, Wash., asslgnor to Crown Zellerbach Corporation, San Francisco, Calif a cororation of Nevada 0 Drawing. Continuation of application Ser. No. 443,083, Mar. 26, 1965. This apllcatlon Feb. 13, 1967, Ser. No. 617,012 The portion of the term of the patent subsequent to Sept. 27, 1983, has been dlsclaimed 14 Claims. (Cl. 424-287) ABSTRACT OF THE DISCLOSURE Synergistic biocidal compositions comprising (i) chlorinated and brominated levulinic acid compounds (with up to four halogen substitutions), including the free acid, alkali metal salts, alkaline earth metal salts, ammonium 20 salts, heavy metal salts, amine salts, phenyl and lower alkyl amides, and alityi esters thereof; and (2) monohydric phenols and dihydric phenols with and without nitro, halo, alkyl, and/or phenol substitutions in ratios of between about 1/20 and 20/ I. The use of such combina- 25 tions in slime control, wood preservation, industry and agriculture is described.

This application is a continuation of Ser. No. 443,083. 30 filed Mar. 6, 1965, which in turn is a continuation-in-part of Ser. No. 135,709, filed Aug. 24, i961, both of which are abandoned.

This invention relates to synergistic compositions and methods for controlling the growth and propagation of microbiological organisms including algae, bacteria, yeasts, and fungi.

In my application, Ser. No. 135,709, is disclosed the versatile and potent biocidai activity of halogenated levulinic acids and their derivatives and the techniques of their formulation into biocidal compositions and use as bioeides.

The present invention stems from my discovery that these halogenated levulinic acid compounds coact synerglstically with certain well-known biocidal agents to produce a biocidal result markedly greater than that achieved when the agents are used separately.

It is accordingly an object of this invention to provide synergistic biocidai compositions which are more effective than the agents when employed alone and which are thereby more economical in use than employment of the agents separately, and their methods of use.

In general, the class of biocides I have found which combine with halogenated levulinic acid compounds to achieve the synergistic results of this invention are phenol and substituted phenols, particularly nitro and halo, alkyl and phenyl substituted phenols.

As used herein, the terms "synergism" is intended to include an increased spectrum of activity (i.e., activity against a larger number of microorganisms) and/or increased activity (i.e., greater activity against specific microorganisms than that obtained by use of either agent alone). Both of these factors play an important role in the economy and commercial acceptance of a biocide. Increased activity of the combination permits the use of smaller amounts of blocldes to achieve satisfactory control with resulting economies. Increasing the spectrum of activity permits wider use of the biocide in environments containing many and diverse microorganisms which must be controlled.

The specific halogenated levulinic acid compounds which are suitable in the synergistic compositions of this invention include those having the formula:

Where R is either chlorine, bromine, or hydrogen and at least one occurrence of R and as many as four occurrences of R, are either bromine and/or chlorine. The derivatives of these acids include the salts, esters, and amides.

Suitable salts include the alkali metal salts, the alkaline earth metal salts, the ammonium salts, the heavy metal salts, and the amine salts. Exemplary of the heavy metal salts are the lead, copper, zinc, nickel, cadmium, chromium, and mercury salts. Exemplary of the alkali and alkaline earth metal salts are the sodium, potassium, calcium, magnesium, strontium, and barium salts. Exemplary of the amine salts are primary methyl amine, dimcthyl amine, primary ethyl amine, and diethyl amine. Illustrative of suitable ester derivatives of the halogenated levulinic acid are the methyl, ethyl, propyl and higher aliphatic and/or aromatic esters such as hexyl, octyl, decyl, and phenyl.

Illustrative of suitable amide derivatives are the N-methyl, N,N-dimethyl, N-ethyl, N,N-diethyl, and N- phenyl amides. For example, N,N-dimethyl 3,5-dichloroievuiinamlde and N-phenyi 3,5-dichlorolevulinamide.

Especially useful in the synergistic compositions of this invention are the chlorinated levulinic acids, particularly 3,3,5-trichloroievulinic acid, 3,5,5-trichlorolevulinic acid, 3,3,3,S-tctrachlorolevulinic acid and 3,5-dichloroievulinic acid, as well as their lower alkyl esters.

The foregoing biocidal agents may be used singly or in combination with each other in the synergistic compositions of the present invention.

The phenols which are suitable in the synergistic compositions of the present invention include those having the formula:

Oil

Where R is selected from the group consisting of alkyl groups having from one to ten carbon atoms and phenyl', X is selected from the group consisting of chloro, bromo and nitro, a is 0 or i; b is 0, l or 2 and c is an integer from 0 to $(a+b) with no more than a total of three nitro groups.

Also suitable,- particularly for aqueous compositions and systems, are the sodium and potassium salts of the above phenols.

Aralkyi substituted phenols such as hexachiorophene may also be employed in the compositions of this invention.

The phenols are well-known and described in the prior art. Many are realily available commercially as biocides.

Monohydric phenol and the dihydric phenols, pyrocatechol, resorcinol and hydroquinone, are useful in the present compositions but, as is recognized in the art, their blocidsl activity may be enhanced by substituting various inorganic and organic groups for one or more ring hydrogen. These substituted phenols are usually preferred in thepresent synergistic compositions.

Illustrative of the chlom-, bromoand nitro-substituted phenols are:

ortho, meta and para monochloroand monobromophenol 2,4-dichloroand 2,4dibromophenol 2,4,6-trichloroand 2,4,6-tribromophenol ortho, meta and para cresol ortho, meta and para ethylphenol ortho, meta and para n-propylphenol ortho, meta and para n-hexylphenol ortho, meta and para n-nonylphenol 2,4-di-n-hexylphenol 1,2-n-nonyl-4-methylphenol 2,3-; 2,4-; 2,5-; 2,6-; 3,4-; and 3,5-xylenol Illustrative of phenols having more than one type of substitution are: 0

3-methyl-2,4,6-trinitrophenol 1-methyl-3-nitrophenol 2-methyl-4,6-dinitrophenol 3-methyl-4-chlorophenol Z-methyl tetrabromophenol Z-methyl tetrachlorophenol 2-chloro-4-phenylphenol 4-chloro-2-phenylphenol 6-chloro-2-phenylphenol Illustrative of substituted dihydric phenols are:

3-hydroxy-4-ethyl phenol 3-hydroxy-4-n-octyl phenol 3-hydroxy-4-chlorophenol 3-hydroxy-4-bromophenol 3-hydroxy-2,4,6-chlorophenol 3-hydroxy-2,4,6 bromophenol 2-hydroxy-4-phenylphenol 3-hydroxy-4-methyl-6-nitrophenol Illustrative of the phenol and substituted phenol salts are:

sodium 2,4,5-trichlorophenate sodium 2,3,4,6-tetrachlorophenate sodium O-phenylphenate sodium pentachlorophenate potassium phenate potassium 2,4-dinitrophenate No particular proportion or range of proportions of halogenated levulinic acid compound to phenol compound is critical to achieving the synergism of this invention. Proportionately minor amounts of either active agent may be utilized with useful results. For example, ratios of both 1 to 20 and 20 to 1, halogenated levulinic acid compound to phenol compound, have actvity greater than either constituent used separately in concentrations equal to the total concentration of the combination. However, maximum activity may generally be obtained where the ratio of halogenated levulinic acid compound to phenol compound is from about 1 to 1 to about 1 to 3.

The compositions of this invention may be applied to the situs of the microorganism to be controlled in keeping with one of the familiar methods of application of hiocides. Hence, they may be diluted with inert diluents, such as talc, and applied in the form of a powder. They may be dispersed in a suitable liquid vehicle, such as an aqueous medium or organic solvent. The compositions are particularly suited for application by means of an aqueous medium or organic solvent.

The suitable concentration of active biocide and the amount required for control will depend upon the type of diluent, the character of the microorganism to be controlled and the character of the substrate on or in which the microorganism is located. Generally, concentrations 75 at the situs of 0.001 to 1% by weight of total biocide (halogenated levulinic acid compound plus phenol) is satisfactory. For various purposes as in aqueous systems such as used in recirculating water systems or for use in agricultural sprays, concentrations as low as 5 to 400 parts per million may be effective in controlling microorganisms. For various uses, concentrated compositions such as from 1% to 50% of active biocide may be desirable, for example in wood impregnation by pressure techniques. They may also 'be used as convenient concentrates for application in water systems or in water sprays. For this purpose surfactants such as lignin sulfonic acid salts may be included in the concentrate.

Suitable organic liquid vehicles are those in which both biocidal components may be dissolved or emulsified. Illustrative are dimethyl sulfoxide, dimethyl formamide, the lower aliphatic alcohols, such as methanol, ethanol and isopropanol, and aliphatic acids such as acetic and propionic acids. The alcohols, however, are desirably combined with the composition at least Within a day or two before use as they may impart a relatively short shelf life to the biocidal composition after they are combined therewith.

Suitable solid vehicles with which the biocidal agents maybe compounded comprise those inert materials which lend themselves to the compounding of powders and dust, including diatomaceous earth, bentonite, talc, bark powder, wood flour, lignin sulfonic acid salts, and the like.

The synergistic biocidal compositions have many important applications including, for example, use as industrial and household germicide, as wood preservative, rot proofing agents for fabrics, use as an agricultural spray, as slime preventatives for use in paper mill pulp slurries and other recirculating water systems, and as a preservative of plastics subject to rot.

The synergistic compositions may be used as household or industrial disinfectants or agricultural sprays advantageously by dissolving or emulsifying the halogenated levulinic acid compound and phenol compound in a suitable organic solvent or water to provide a liquid disinfectant which maybe applied to the surfaces to be disinfected in the usual manner. For this purpose, a concentration of 5 to 400 parts per million may be effective in destroying the microorganisms contacted.

Where the compositions are employed as a wood preservative, they may first be dissolved in a lower aliphatic alcohol or other organic liquid vehicle with good wood penetrant properties to form a solution having a concentration of from 0.1% to 50% by weight of total biocide (including both constituents). This then may be applied to the wood by brushing or dipping or by using the conventional pressure treatment.

Where the compositions are to be employed as a rotproofing compound for application to cotton and other fabrics subject to fungal attack, the cloth may be impregnated with a solution of the biocides in dimethyl sulfoxide, lower aliphatic alcohol or other liquid vehicle by immersion or spraying, using an application of from 0.25% to 5% by weight, total combined biocide basis.

Where the synergistic biocide combinations are to be employed in recirculating water systems to prevent slime formation, as for example, in spray towers or in papermaking slurries, from 5 to 400 parts per million of combined agent may be added to the system in the form of an alcohol solution or an aqueous emulsion. The phenol compound and halogenated levulinic acid compound may each be added separately or in the same medium to the water but preferably the phenol compound is added to a concentration of at least 8 parts per million and the halogenated levulinic acid compound is added to a concentration of at least 2 parts per million. However, in water systems having lower concentrations of slime nutrients as in spray towers or in paperniaking slurries downstream from the beater, concentrations of around 0.5 part per million total combined biocide may give satisfactory control.

The synergistic compositions of this invention and their application are illustrated in the following examples:

Example l.-Slimicide compositions Comparisons were made of relative biocidal activity against slime organisms of chloroand nitro-substituted phenols combined with 3,3,5-trichlorolevulinic acid in varying proportions but with a constant total biocide concentration. These in turn were compared with the biocidal activity of each individual biocide when applied alone in g the same concentration.

A papermaking ground wood pulp slurry at 0.3% consistency, contaminated principally with Aerobacter acrogencs, held at 25 C. and constantly stirred was used for the evaluation. In each test, except for a control and for comparisons of 3,3.5-trichlorolevulinic acid alone at 25 parts per-million, 50 parts per million and 75 parts per million, the total active biocide concentration used was 100 parts per million. Activity-in each test was measurctt by withdrawing an aliquot at the end of one hour and at the end of twenty-four hours from the time of addition of the biocide, plating each aliquot using Sabourauds Dextrose agar. incubating the plate at 30 C. for twenty-four hours and couning the slime organisms. In each test the biocides were added to the pulp slurry as a 20% ethanol solution prepared immediately before the test. The results are shown in Table I:

TABLE I Bloeldes Bloeide Total Bllme Organism Count- Ratio Bioeido (AIB) Concen- A B trution After 1 hr. After 24 hrs.

p.p.m.

MC 100 101000 ltXLiXiO MOP TCLA 26/75 100 128 1 MC? TOLA.-. 60/50 100 30 1 MCP.. 'iCLA 75/28 100 13 1m IMJXX) 101000 it!) 104 l 100 ZZT) 0 concentration. FOP-6x81111316, when 100 parts per million .of pentachlorophenol was-used alone,=there wasa slime organism count of over 100,000 after one hour-contact, whereas. when used with 3,3,5-trlchiorolevulinic acid at l00-parts;per million total concentration in aratio of 75/25, there is total kill and in a ratio of 50/50 there was an organism count-of 3.

Example 2.Wood preservative composition Compositions for use as a wood preservative may be prepared as follows:

Sodium 3,5-dichlorolevulinate 40 Sodium pentachlorophenate 60 These ingredients are dissolved to 5% by weight in 50/50 ethanol-water and the composition may be painted on the wood surfaces and allowed to soak in and dry.

Example 3.Antiseptic composition 12.5 grams of hexachlorophene and 0.5 gram of 3,3,5- trichlor'olevulinic acid may be dissolved in grams of ethanol. This solution may be applied to the skin including wounds' to control staphylococcus and other microorganism infections.

Example 4.-Household germicide composition 3 hydroxy 4 octylphenol and 3,3,5 trichlorolevulinic acid are combined in dimethyl sult'oxide containing a non-ionic surfactant to provide a household germieide having both bioeidal and detergent properties. A suitable formulation comprises:

Grams 3 hydroxy 4 octyiphenol 5 3,3,5 trichlorolcvulinic acid 5 Dimethylsulfoxide 4O Triton X-l00 5 Pigment Green MX (colorant to esthetic appeal) Pigment Green MX is a standard well known commercially available dye consisting of nitrosated 2 naphthol- 6 sulfonic acid adducted to ferrous sulfate. Triton X400 is the trade name for a non-ionic wetting agent, namely, an alkyl aryl polyether alcohol, available from Rohm and Haas.

Example S.-Composition for water treatment The following formulation is useful for treatment of industrial waters contaminated with algae and bacteria. This concentrate .may be added to the water preferably with sufiicient agitation to achieve adequate distribution. Addition to a concentration of 10 parts per million to 25 parts per million total biocide is recommended:

Dimethyl sulfoxide -..(by weight)..- 100 Sodium O-phenylphenate do 40 3.3,5.- trichlorolevulinic acid do... 10 Cuprous chloride do- 1 Orzan AL-SO --do 100 Water solution of ammonium lignln sulfonate (00% solids) Crown Zellerbach Corporation.

The composition may be blended by stirring together of all components except the Orzan AL-50 until uniform.'The Orzan AL-50 is then blended in to give a concentrate readily dispersible in water.

Example 6.-Plastic additive composition 4,6 dibromo O cresol and ethyl 3.5 dichlorolevulinate is formulated in proportion of 5% by weight, each, in dioctyl phthaiate. This composition may be incorporated on a 2-roll mill, like a normal plasticizer, with various polymers, such as vinyls, subject to mold growth.

Example 7.-Composition for wood treatment Wood preservative grade creosote, obtained from coal tar distillation and containing various alkylated phenols, is combined with chlorinated levulinie acid (7% 3,3,5,5- tetrachloroievulinic acid and 97% trichlorolevulinic acid) inratio of 9 to l in a xylcne-propyl alcohol combination solvent. This composition may be impregnated, for example, into one inch square Douglas fir posts at 13 pounds of oven dry impregnant per square foot of surface to provide superior resistance to rot when the stakes are implanted in soil than lsachieved by creosote impregnation alone at the same level of treatment (total .blocide).

. What is claimed is:

1. A synergistic biocidal composition comprising as biocidally active components thereof the combination of (A) at least one chlorinated levulinic acid compound from the group consisting of A 011-- it? kt wherein R is selected from the group consisting of alkyl groups having from one to ten carbon atoms and phenyl; X is selected from the group consisting of chloro, bromo and nitro, a is or 1; b is 0, l, or 2, and c is an integer from 0 to S-(a-i-b) with no more than a total of three being nitro groups; (b) the sodium and potassium salts thereof; and (c) hexachlorophene the proportion of said halogenated levulinic acid compound to said phenol compound being from about 1/20 to about 20/ 1. 2. A composition as in claim 1 and including a dilueat.

3. A composition as in claim 1 and including a surfactant.

4. The method of controlling microbiological organisms which comprises applying to the situs of such organisms an effective concentration of a synergistic biocidal composition as in claim 1.

5. A synergistic biocidal composition as in claim 1 and wherein said chlorinated levulinic acid compound is selected from the group consisting of (a) 3,3,5-trichlorolevulinic acid;

(b) the alkali, alkaline earth metal and heavy metal salts thereof; and

(c) the lower alkyl esters thereof; said phenol compound is selected from the group consisting of (a) phenols having the formula wherein X is selected from the group consisting of chloro, bromo and nitro and c is an integer from 1 to 5 with no more than total of three being nitro groups; and

(b) the sodium and potassium salts thereof;

and said composition includes a carrier.

6. A composition as in claim 5 and wherein the proportion of halogenated levulinic acid compound to phenol compound is from about l/l to about l/3.

7. The method of controlling microbiological organisms which comprises applying to the situs of such organisms an effective concentration of a composition as in claim 5.

8. The method of controlling slime-producing microbiological organisms in aqueous systems which comprises adding to said system an effective concentration of a composition as in claim 5.

9. The method of preserving wood which comprises applying to said wood an effective concentration of a composition as in claim 5.

10. A composition for use as an agricultural spray, disinfectant or the like comprising a composition as in claim 5 in a concentration of between about 5 parts per million and 400 parts per million in an aqueous mediurt:r;,.-.

11. A synergistic biocidal composition as in claim 1 and wherein said chlorinated levulinic acid compound is selected from the group consisting of (a) 3,3,5-trichlorolevulinic acid;

(b) the alkali metal, alkaline earth metal and heavy metal salts thereof; said phenol compound is selected from the group consisting of (a) phenols having the formula wherein R is selected from the group consisting of alkyl groups having from one to ten carbon atoms phenyl; and (b) the sodium and potassium salts thereof; and said composition includes a carrier.

12. A method of preserving wood which comprises ap plying to said wood an effective concentration of a composition as in claim 11.

13. A synergistic biocidal composition as in claim 1 and wherein said chlorinated levulinic compound is 3,3,5-trichlorolevulinic acid; said phenol compound is selected from the group consisting of phenol, Z-monochlorophenol, 4-monochlorophenol, 2,4-dichlorophenol, 2,4,6- trichorophenol, 2,4-dinitrophenol, pentachlorophenol, pentabromophenol, Z-phenyl phenol, 2-phenyl-4-chlorophenol, m-cresol, 2,4,6-trinitrocresol, 4-tert. butyl catechol, hexachlorophene, and the sodium and potassium salts thereof; and said composition includes a carrier.

14. The method of controlling slime-producing microorganisms in papermaking slurries which comprises adding to the slurry, in an effective amount, 3,3,5-trichlorolevulinic acid and a phenol compound selected from the group consisting of phenol, -monochlorophenol, 4-monochlorophenol, 2,4-dichlorophenol, 2,4-6-trichlorophenol, 2,4-dinitrophenol, pentachlorophenol, pentabromophenol, Z-phenyl phenol, 2-phenyl-4-chlorophenol, m-cresol, 2,4,6-trinitrocresol, 4-tert. butyl catechol, hexachlorophene, and the sodium and potassium salts thereof, said 3,3,5-trichlorolevulinic acid and said phenol compound being added to the slurry in the proportion of between about l/20 to 20/1.

References Cited Merck Index, 7th ed., 1960, pp. 675-676. Frear, Chemistry of the Pesticides, 3rd ed., 1955, pp. 290294 and 308.

FRANK CACCLAPAGLIA, IR., Primary Examiner.

S. FRIEDMAN, Assistant Examiner.

US. Cl. X.R. 

